Effects Of Nerve Growth Factor On The Myocardial Cells And Sympathetic Nerve Of Non-infarcted Zone In A Rabbit Model Of Healed Myocardial Infarction

Sympathetic hyperinnervation in healed-infarction is an important factor for triggering ventricular arrhythmias by binding to p75NTR, which is thought to be due to sudden cardiac death during the post-infarction period. We examined the effect of NGF and p75NTR on the action potential in cardiomyocytes.The first part Effects of Nerve Growth Factor on the Ventricular Fibrillation Threshold and the Distribution of Sympathetic Nerve in a Rabbit Model of Healed Myocardial InfarctionMethods:Forty rabbits were divided into four groups as HMI group, p75 NTR activation group, p75 NTR inhibition group and the sham group. Rabbits with occlusion of the left circumflex coronary artery were prepared and allowed to recover for ten weeks. The VFTs in rabbit heart with HMI and sham group were studied. The distribution and densities of S-100 protein and tyrosine hydroxylase(TH) in ventricle were detected with immunohistochemical technique.Results:The VFT of p75 NTR activation group were lower significantly than those of HMI and sham groups. Comparing with those in sham and HMI groups, the distribution of sympathetic nerve fibers in p75 NTR activation group increased significantly (P<0.05). The distributions of nerve fibers in p75 NTR inhibition group were significantly reduced than those of p75 NTR activation and HMI groups.Conclusions:The VFT decreased and the densities of sympathetic nerve increased in the noninfarcted myocardium in a rabbit model of healed Myocardial Infarction. NGF is essential for enhanced sympathetic hyperinnervation and decreased VFT that may be mediated by binding to p75NTR in a rabbit model of healed Myocardial Infarction. These changes were partly reversed by p75 NTR inhibition.The second part Effects of Nerve Growth Factor on the Action Potential Duration and Repolarizing Currents in a Rabbit Model of Healed Myocardial InfarctionMethods:Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (HMI group). During ligation surgery of the left coronary artery, a polyethylene pipe was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/day for eight weeks (HMI+NGF group). Cardiomyocytes were isolated from regions of the noninfarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps.Results:The lengthening of the APD was more notable after NGF infusion than that of the HMI and control cardiomyocytes. Current amplitudes of Ito in HMI+NGF cardiomyocytes were markedly smaller than that in HMI and control cardiomyocytes. Current calcium amplitudes (ICa, L) in HMI+NGF cardiomyocytes were significantly increased than other groups. Current amplitudes of IKr in the HMI cardiomyocytes with NGF treatment were smaller than those of the HMI and control cardiomyocytes. Compared with the HMI group, the current amplitudes of IKs from NGF treated HMI cardiomyocytes were significantly smaller.Conclusion:After infusion of NGF, APD in a rabbit model of healed Myocardial Infarction would be prolonged. This due to that Ito,IKr and IKs were decreased, and that Ica, L were significantly increased.